Rats will receive injections of kainic acid into the brain, in the region of the ventral pallidum. Such injections result in a depletion of acetylcholine-related enzymes in the cerebral cortex. The neurochemical changes parallel those seen in patients who have died with Alzheimer's dementia. At varying time points following the surgery, the rats will be tested in cages equipped with infrared photocell beams to detect locomotor activity. This measure of activity will be taken for two hours prior to drug injection and for two hours after drug injection for each rat. The rats will receive subcutaneous injections of nicotine sulfate and of other drugs. Differences in responsiveness to the drugs between kainic acid lesioned animals and control animals will be the major focus of the research. Differences in responsiveness to nicotine in rats with these lesions have already been found, and they imply that nicotinic cholinergic receptors in the cortex may have become hypersensitive as a result of denervation. Since patients suffering from Alzheimer's dementia also have decreased cholinergic innervation to the cerebral cortex, they may also be hyperresponsive to the behavioral effects of nicotine. Thus, this animal model may provide a basis for developing a specific diagnostic test for Alzheimer's dementia. These experiments also provide a further test of this animal model of Alzheimer's disease and may lead to an increased understanding of the nuerochemical changes occurring in the disease. If Alzheimer's patients are shown to have an increased sensitivity to nicotine, then it might also be the case that nicotinic hypersensitivity mediates at least some of the clinical symptoms of the disease. Drug treatments could be devised that would correct the hypersensitivity and perhaps alleviate some of the symptoms.